DIETARY MONOUNSATURATED FATTY-ACIDS PROMOTE AORTIC ATHEROSCLEROSIS INLDL RECEPTOR-NULL, HUMAN APOB100 - OVEREXPRESSING TRANSGENIC MICE

In mice with genetically engineered high levels of plasma low density lipoprotein (LDL), we tested the hypothesis that an increase in the di etary content of monounsaturated fatty acids but not of polyunsaturate d fatty acids would promote atherosclerosis. The mouse model used was an LDL receptor-null, human apoB100-overexpressing strain. Six experim ental groups of 19 to 38 mice of both sexes were established when the animals had reached 8 weeks of age. For the next 16 weeks, individual groups were fed either a commercial diet or prepared diets including f at as 10% of energy, with 5 different fatty acid enrichment patterns i ncluding the following: saturated (sat), cis and trans monounsaturated (mono), and n-3 and n-6 polyunsaturated (poly). Highly significant di fferences (ANOVA, P<0.0001) in LDL cholesterol (in mg/dL) were found, with the rank order at 16 weeks being trans mono (mean, 1390)>sat (922 ) =cis mono (869)=n-6 poly (868)>n-3 poly (652)>commercial diet (526). Significant elevations in very low density lipoprotein cholesterol we re also found in the trans and cis mono and sat,groups, and triacylgly cerol concentrations were also elevated in all groups. High density li poprotein cholesterol concentrations were consistently low (20 to 50 m g/dL) in all groups. Highly significant differences (ANOVA, P<0.0001) in atherosclerosis, quantified by measurement of aortic cholesteryl es ter concentration (mg/g protein) among dietary fatty acid groups were found, with the order being trans mono (mean, 50.4)>sat (35.6)=cis mon o (34.6)>n-6 poly (18.3)=n-3 poly (9.7)=commercial diet (7.8). Therefo re, in this mouse model of hypercholesterolemia, dietary cis or trans monounsaturated fat did not protect against atherosclerosis developmen t, whereas aortic atherosclerosis in either of the polyunsaturated fat groups was significantly less than in the saturated fat group.